Cancer can occur in any tissue of the body. It results from a change in certain cells that causes them to evade the normal growth limiting mechanisms, i.e., to no longer be under the feedback controls that normally stop cellular growth and reproduction after a given number of such cells have developed. Cell division and transcription are highly coordinated processes that play important roles in this feedback control. See, e.g., Beeson, et al. (eds.) (1979) Textbook of Medicine, 15th ed., W. B. Saunders Co., Philadelphia, Pa.; and DeVita, et al. (eds.) (1993) Cancer: Principles and Practice of Oncology, 4th ed., Lippincott, Philadelphia, Pa.
Molecules which function to regulate transcription and cell division play important roles in the controlled growth of various types of cells. Aberrations in these controls can lead to various disease states, e.g., oncogenesis, inappropriate immune responses to infections, improper wound healing, developmental abnormalities, and metabolic problems.
The cell cycle can be divided into four phases: the presynthetic phases (G.sub.0 and G.sub.1); the phase of DNA synthesis (S); and the postsynthetic phase (G.sub.2). See, e.g., Guyton (ed.) (1976) Textbook of Medical Physiology, 5th ed., W.B. Saunders Co., Philadelphia, Pa.; Alberts, et al. (eds.) (1994) Molecular Biology of the Cell, 3rd ed., Garland Publishing, New York, N.Y.; and Darnell, et al. (eds.) (1990) Molecular Cell Biology, 2nd ed., W. H. Freeman, New York, N.Y. Effective chemot herapeutic agents are often those which target diseased cells in the S phase, e.g., choriocarcinoma, acute lymphocytic leukemia, lyphocytic lymphosarcoma, Burkitt's lymphoma, Hodgkin's disease, testicular neoplasms, Wilm's tumor, and Ewing's sarcoma. Unfortunately, oncogenic cells not actively dividing are less sensitive to these agents.
In the immune system, many of the effects of known cytokines on gene transcription are known to be mediated by cytokine inducible DNA binding proteins. See, e.g., Paul (ed.) (1994) Fundamental Immunology, 3rd ed., Raven Press, New York, N.Y. In particular, the family of Interferon Regulatory Factors (IFN), which are present in the promoters of interferon (IFN) genes, includes both activators and repressors of transcription. IFN mediated gene regulation is a complex cascade of events that leads, e.g., to acquisition of an antiviral state.
The lack of knowledge regarding the control of the cell cycle or transcriptional elements has hampered the ability of medical science to specifically regulate cell division or immune responses. The present invention provides compositions which will be important in the control of cell division and transcription.